Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triple A syndrome is a rare autosomal recessive disorder characterized by ACTH-resistant adrenal failure, alacrima, achalasia, and progressive neurological manifestations. The majority of cases are associated with mutations in the AAAS gene, which encodes a novel, 60-kDa WD-repeat nuclear pore protein, alacrima-achalasia-adrenal insufficiency neurological disorder (ALADIN) of unknown function. Our aim was to elucidate the functional role of ALADIN by determining its interacting protein partners using the bacterial two-hybrid (B2-H) technique. Nonidentical cDNA fragments were identified from both a HeLa S-3 cell and human cerebellar cDNA library that encoded the full-length ferritin heavy chain protein (FTH1). This interaction was confirmed by both co-immunoprecipitation and fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer studies. Immunoblotting showed that fibroblasts from triple A patients (with known AAAS mutations) lack nuclear FTH1, suggesting that the nuclear translocation of FTH1 is defective. Cells transfected with FTH1 and visualized by confocal microscopy had very little nuclear FTH1, but when cotransfected with AAAS, FTH1 is readily visible in the nuclei. Therefore, FTH1 nuclear translocation is enhanced when ALADIN is coexpressed in these cells. In addition to its well known iron storage role, FTH1 has been shown to protect the nucleus from oxidative damage. Apoptosis of neuronal cells induced by hydrogen peroxide was significantly reduced by transfection of AAAS or by FTH1 or maximally by both genes together. Taken together, this work offers a plausible mechanism for the progressive clinical features of triple A syndrome.
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PMID:Deficiency of ferritin heavy-chain nuclear import in triple a syndrome implies nuclear oxidative damage as the primary disease mechanism. 1985 93

Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal inflammatory disease that is becoming more widely recognized as a cause of feeding difficulties in infants and young children, as well as gastroesophageal reflux disease (GERD)-like symptoms, dysphagia, and food impaction in children and adolescents. The diagnosis of EoE is clinicopathologic, based on endoscopic, histologic, and clinical findings. Patients with suspected eosinophilic esophagitis require an endoscopy with biopsies. The diagnosis requires the presence of 15 or more intraepithelial eosinophils/HPF in at least one endoscopic esophageal mucosal biopsy. Histology will reveal mucosal eosinophilia isolated to the esophagus, which does not improve following Proton Pump Inhibitor (PPI) trial. Other disorders causing esophageal eosinophilia, such as GERD, celiac disease, Crohn's disease, infection, hypereosinophilic syndrome, achalasia, and drug hypersensitivity must be ruled out. The goals of treatment should include both histologic healing of the esophageal mucosa, as well as resolution of clinical symptoms. Treatment options include food elimination diets, topical steroids, and/or esophageal dilatation. While the understanding of EoE has evolved over the past twenty years, it continues to be a challenging diagnosis due to the clinical and histopathologic similarities to GERD. Much remains to be studied regarding the underlying pathology, as well as appropriate biomarkers to better evaluate response to therapy.
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PMID:Pediatric Eosinophilic Esophagitis. 3011 May 27